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Article: Exome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey

TitleExome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey
Authors
Issue Date2018
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/npjgenmed/
Citation
npj Genomic Medicine, 2018, v. 3, Article no. 19 How to Cite?
AbstractCurrently, offering whole-exome sequencing (WES) via collaboration with an external laboratory is increasingly common. However, the receipt of a WES report can be merely the beginning of a continuing exploration process rather than the end of the diagnostic odyssey. The laboratory often does not have the information the physician has, and any discrepancies in variant interpretation must be addressed by a medical geneticist. In this study, we performed diagnostic WES of 104 patients with paediatric-onset genetic diseases. The post-exome review of WES reports by the clinical geneticist led to a more comprehensive assessment of variant pathogenicity in 16 cases. The overall diagnostic yield was 41% (n = 43). Among these 43 diagnoses, 51% (22/43) of the pathogenic variants were nucleotide changes that have not been previously reported. The time required for the post-exome review of the WES reports varied, and 26% (n = 27) of the reports required an extensive amount of time (>3 h) for the geneticist to review. In this predominantly Chinese cohort, we highlight the importance of discrepancies between global and ethnic-specific frequencies of a genetic variant that complicate variant interpretation and the significance of post-exome diagnostic modalities in genetic diagnosis using WES. The challenges faced by geneticists in interpreting WES reports are also discussed.
Persistent Identifierhttp://hdl.handle.net/10722/260556
ISSN
2017 Impact Factor: 3.467
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMak, CCY-
dc.contributor.authorLeung, KC-
dc.contributor.authorMok, TKG-
dc.contributor.authorYeung, KS-
dc.contributor.authorYang, W-
dc.contributor.authorFung, CW-
dc.contributor.authorChan, HSS-
dc.contributor.authorLee, SL-
dc.contributor.authorLee, NC-
dc.contributor.authorPfundt, R-
dc.contributor.authorLau, YL-
dc.contributor.authorChung, BHY-
dc.date.accessioned2018-09-14T08:43:39Z-
dc.date.available2018-09-14T08:43:39Z-
dc.date.issued2018-
dc.identifier.citationnpj Genomic Medicine, 2018, v. 3, Article no. 19-
dc.identifier.issn2056-7944-
dc.identifier.urihttp://hdl.handle.net/10722/260556-
dc.description.abstractCurrently, offering whole-exome sequencing (WES) via collaboration with an external laboratory is increasingly common. However, the receipt of a WES report can be merely the beginning of a continuing exploration process rather than the end of the diagnostic odyssey. The laboratory often does not have the information the physician has, and any discrepancies in variant interpretation must be addressed by a medical geneticist. In this study, we performed diagnostic WES of 104 patients with paediatric-onset genetic diseases. The post-exome review of WES reports by the clinical geneticist led to a more comprehensive assessment of variant pathogenicity in 16 cases. The overall diagnostic yield was 41% (n = 43). Among these 43 diagnoses, 51% (22/43) of the pathogenic variants were nucleotide changes that have not been previously reported. The time required for the post-exome review of the WES reports varied, and 26% (n = 27) of the reports required an extensive amount of time (>3 h) for the geneticist to review. In this predominantly Chinese cohort, we highlight the importance of discrepancies between global and ethnic-specific frequencies of a genetic variant that complicate variant interpretation and the significance of post-exome diagnostic modalities in genetic diagnosis using WES. The challenges faced by geneticists in interpreting WES reports are also discussed.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/npjgenmed/-
dc.relation.ispartofnpj Genomic Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleExome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey-
dc.typeArticle-
dc.identifier.emailLeung, KC: gleungkc@hku.hk-
dc.identifier.emailYeung, KS: ksyyeung@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.emailFung, CW: fcw1209m@hkucc.hku.hk-
dc.identifier.emailChan, HSS: sophehs@hku.hk-
dc.identifier.emailLee, SL: slleem@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailChung, BHY: bhychung@hku.hk-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authorityChan, HSS=rp02210-
dc.identifier.authorityLau, YL=rp00361-
dc.identifier.authorityChung, BHY=rp00473-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41525-018-0056-5-
dc.identifier.hkuros290098-
dc.identifier.volume3-
dc.identifier.spageArticle no. 19-
dc.identifier.epageArticle no. 19-
dc.identifier.isiWOS:000453881400001-
dc.publisher.placeUnited Kingdom-

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